| Autor: |
Adnan Kastrati, Wu Yin, Jeanette Erdmann, Ruth J. F. Loos, Paul L. Auer, Susanne Moebus, Christina Willenborg, Piera Angelica Merlini, Jochen Kruppa, Anubha Mahajan, Julian C. van Capelleveen, Christa Meisinger, Charles Kooperberg, Natalie R. van Zuydam, Domenico Girelli, Erik P A Van Iperen, Rebecca D. Jackson, Tom R. Webb, Dan M. Roden, Ursula M. Schick, Colin N. A. Palmer, Eli A. Stahl, Mark I. McCarthy, Andres Metspalu, David-Alexandre Trégouët, Markus Perola, Kathleen Stirrups, G. Kees Hovingh, Martina Mueller-Nurasyid, Maris Alver, Christopher Newton-Cheh, Daniel J. Rader, Karl-Heinz Joeckel, Karen O. Akinsanya, Nilesh J. Samani, Alistair S. Hall, Stefano Duga, Louise A. Donnelly, J. Wouter Jukema, Nour Eddine El-Mokhtari, Rosanna Asselta, Tibor V. Varga, Heribert Schunkert, Erwin P. Bottinger, Paola G. Ferrario, Nathan O. Stitziel, Nicola Marziliano, Marie-Pierre Dubé, Andre Franke, Robert A. Scott, Thomas Meitinger, Stavroula Kanoni, Jan-Håkan Jansson, Christian Hengstenberg, Svati H. Shah, Josh C. Denny, Melanie Waldenberger, Alex S. F. Doney, Nicola Martinelli, Cristen J. Willer, Olle Melander, Hugh Watkins, He Zhang, Inke R. Koenig, Ron Do, Thomas F. Vogt, Chunyu Liu, Omri Gottesman, Kari Kuulasmaa, Peter S. Braund, Praveen Surendran, Dermot F. Reilly, Per Hoffmann, Georg Ehret, Karl L. Laugwitz, Diego Ardissino, Børge G. Nordestgaard, Joanna M. M. Howson, Raimund Erbel, Stefan A. Escher, Wolfgang Lieb, Hong-Hee Won, Majid Nikpay, Martin Farrall, Stefanie Heilmann, Ruth McPherson, Nicholas G. D. Masca, Evelin Mihailov, Danish Saleheen, Andrew D. Morris, Neil R. Robertson, Oddgeir L. Holmen, Sekar Kathiresan, Annette Peters, Jean-Claude Tardif, Alaa AlQarawi, Frank Kee, Jennifer Kriebel, Panos Deloukas, Anuj Goel, Kristian Hveem, Konstantin Strauch, Alexander P. Reiner, Paul W. Franks, John R. Thompson, Robin Young, William E. Kraus, Nicholas J. Wareham, Aldi T. Kraja, Rajiv Chowdhury, Oliviero Olivieri, Folkert W. Asselbergs, Adam S. Butterworth, Daniel I. Chasman, Gina M. Peloso, Peter Weeke, Christian M. Shaffer, Naveed Sattar, Muredach P. Reilly, John Danesh, Marco M Ferrario, Ian Ford, Lingyao Zeng, Marju Orho-Melander, Louis-Philippe Lemieux Perreault, Tõnu Esko, Eirini Marouli, Thorsten Kessler, Yingchang Lu |
| Přispěvatelé: |
Ehret, Georg Benedikt, Vascular Medicine, Graduate School, ACS - Amsterdam Cardiovascular Sciences |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
New England Journal of Medicine, Vol. 374, No 12 (2016) pp. 1134-1144
New England journal of medicine, 374(12), 1134-1144. Massachussetts Medical Society
New England Journal of Medicine
New England Journal of Medicine, 374(12), 1134. Massachussetts Medical Society
N. Engl. J. Med. 374, 1134-1144 (2016) |
| ISSN: |
0028-4793 |
| Popis: |
BACKGROUND: \ud \ud The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets.\ud \ud METHODS: \ud \ud Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes.\ud \ud RESULTS: \ud \ud We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10(-7)).\ud \ud CONCLUSIONS: \ud \ud We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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